title: The amyloid-cell membrane system. The interplay between the biophysical features of oligomers/fibrils and cell membrane defines amyloid toxicity.
abstract: Amyloid cytotoxicity, structure and polymorphisms are themes of increasing importance. Present knowledge considers any peptide/protein able to undergo misfolding and aggregation generating intrinsically cytotoxic amyloids. It also describes growth and structure of amyloid fibrils and their possible disassembly, whereas reduced information is available on oligomer structure. Recent research has highlighted the importance of the environmental conditions as determinants of the amyloid polymorphisms and cytotoxicity. Another body of evidence describes chemical or biological surfaces as key sites of protein misfolding and aggregation or of interaction with amyloids and the resulting biochemical modifications inducing cell functional/viability impairment. In particular, the membrane lipid composition appears to modulate cell response to toxic amyloids, thus contributing to explain the variable vulnerability to the same amyloids of different cell types. Finally, a recent view describes amyloid toxicity as an emerging property dependent on a complex interplay between the biophysical features of early aggregates and the interacting cell membranes taken as a whole system.
authors.affiliation: Department of Biomedical Experimental and Clinical Sciences and Research Centre on the Molecular Basis of Neurodegeneration, University of Florence, Florence, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cecchi
authors.forename: Massimo
authors.initials: M
authors.lastname: Stefani
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D011487:Protein Conformation; D017510:Protein Folding; D013499:Surface Properties
chemical_list: D000682:Amyloid
keywords: Amyloid; Amyloid oligomers; Amyloid toxicity; Protein aggregation; Protein misfolding